Sample processing system for processing biological samples

ABSTRACT

The invention relates to a sample processing system and method for processing biological samples, comprising a sample processing device having: a receiving plate, which is arranged substantially horizontally in a plane; a first and second working arm, which can move relative to the receiving plate and extend substantially parallel to each other in a second direction (Y) over the receiving plate; at least one pipetting device mounted on the first working arm, which is movable in the second direction (Y) and in a third direction (Z) orthogonal in relation to the first and second direction (X, Y); at least one gripping device, mounted on the second working arm, with grippers that can be rotated around a gripper axis of rotation (GA) parallel to the third direction (Z); and a control device for controlling the pipetting device and the gripping device.

This application is a Divisional of Ser. No. 14/390,111 filed Oct. 2,2014, which is a 35 U.S.C. 371 National Phase Entry Application fromPCT/EP2013/060693, filed May 23, 2013, which claims the benefit ofGerman Patent Application No. 10 2012 208 707.9 filed on May 24, 2012,the disclosure of which are incorporated herein in their entirety byreference.

DESCRIPTION

The present invention relates to a sample processing system forprocessing of biological samples, in particular bodily fluids such asblood, saliva, secretions and the like or tissue samples, in particularfor preparation of samples for a DNA analysis by PCR, comprising asample processing device

-   -   with a receiving plate, wherein the receiving plate (14) is        arranged essentially horizontally in a plane defined by a first        and a second direction (X, Y);    -   with a first and a second working arm, wherein the first and        second working arm are movable relative to the receiving plate        along the first direction (X), preferably along a first edge of        the receiving plate, and wherein the first and the second        working arms extend essentially in parallel with respect to each        other in the second direction across the receiving plate,        wherein at the first working arm at least one pipetting device        is attached, which is moveable in the second direction (Y) and        in a third direction (Z) perpendicular to the first and the        second directions, and wherein at the second working arm a        gripping device is attached, which is moveable in the second        direction (Y) and in a third direction (Z) perpendicular to the        first and the second direction, wherein grippers provided on the        gripping device are rotatable around a gripper axis of rotation        parallel to the third direction (Z); and    -   with a control device for controlling the pipetting device and        the gripping device;        a plurality of sample containers, which are filled with samples,        in particular liquid samples, or which can be filled with        samples or reagents,        a plurality of pipetting tips, which can be used by means of the        pipetting device, for aspirating and dispensing of sample liquid        or further reagents necessary for the sample processing, such as        a lysis-buffer,        wherein the sample containers and the pipetting tips are        arranged on the receiving plate by means of corresponding sample        container carriers and pipetting tip carriers, respectively.

An example of such a sample processing system is known from WO2010/056903 A1. Within this known sample processing system, samplecontainer carriers, in which the sample containers are arranged inmatrix form, are submitted manually on a first working plane into thesample processing device. Then, the sample containers are taken outseparately from the sample container carriers by means of a robot arm,which transports a gripped sample container to a barcode reader andconsecutively to a mixing device. After mixing the sample container istransported by another gripper to a holder and fixed therein such thatby means of the gripper a closing cap screwed onto the sample containercan be unscrewed and removed. After opening of the closing cap, theclosing cap is hold by the gripper and by means of a pipetting devicesample liquid is taken out of the sample container and delivered toanother sample container (so-called aliquotation). After pipetting thefirst sample container is closed again and placed back into the samplecontainer carrier. Consecutively, the aliquoted sample runs throughfurther processing steps, such as heating, mixing, pipetting, withregard to the analysis to be performed. The different processing stepsin this system are performed on differing planes, which overlap partly.Further, several different transport devices, such as the robot arm, thegripper and lifting devices, are necessary to move the sample containerwithin the sample process system, in particular to differing planes andinto different process stations such as mixing stations, closingstations. All together, a complicated and nested structure with manyindividual components results, which are necessary for only one specialprocessing step. Further, the arrangement with different planes has thedanger that in case of an exit of biological material because of adefective sampling container or a problem of opening/closing of theclosures and the like all planes lying below are contaminated.

It is an object of the invention to provide a simplified sampleprocessing system and method, through which the disadvantage of knownsystems can be avoided.

To this end, according to a first aspect of the invention it is proposedthat the controlling device of the sample processing device isconfigured such that a sample liquid contained in a sample container, inparticular of liquid biological material or of a mixture of at least onereagent with a biological material to be solved or dissolved, is mixedby the gripping device by rotating a sample container gripped with thegrippers around the gripper axis of rotation, preferably with around 500to 200 revolutions per minute.

The gripper device is hence not only used for transport of samplecontainers, as is the case for the known robot arm, but is additionallyused for mixing of sample liquid, without it being necessary that tothis end a specific mixing device has to be provided within the sampleprocessing system. This simplifies the structure of the sampleprocessing system or the sample processing device, as additionalcomponents can be saved. Further, this allows optimizing processingsteps of the sample processing.

According to a second aspect it is proposed as a further development oralso self-contained that at the at least one gripping device a firstsensor device is attached, which is configured to detect anidentification pattern attached to a sample container, in particularbarcode, wherein the control device is configured to control thegripping device such that a gripped sample container is placed into asample container carrier in a predetermined rotation position relativeto a position, in which the identification pattern has been detected,such that a plurality of sample containers placed by the gripping deviceinto the sample container carrier can be or are aligned with respect tothe respective identification pattern essentially in the same manner.

Providing of a sensor device for detecting an identification patternattached to the sample container allows further optimizing of processflows. Since the sensor device is moved together with the grippingdevice, it is not necessary that the sample container to be processedhas to be moved to a specific position within the sample processingdevice to be able to read the identification pattern. In contrast, suchan identification of a sample container may be performed shortly aftergripping of the sample container and its take-out from the samplecontainer carrier, while the gripping device is already moved to aposition, at which a further processing step for the sample isperformed. As identification pattern barcodes in its various knownrealizations are possible such as one-dimensional barcode, 2D-barcodeand the like. Naturally, also further patterns or signs may be used asidentification patter or may supplement a barcode, such as numerals,letters or the like.

As a further development it is proposed that the sample processingdevice comprises at least one closing device, which is configured suchthat a sample container accommodated in the closing device is detachedfrom a corresponding closing element, such as a cap, stopper or thelike, to open the sample container or is connected with such a closingelement to close the sample container. Preferably, the closing device isformed such that it may perform the detaching of a tightly fixed closingelement, in particular a screw closing element or screw cap and thefixing of such a closing element under use of the corresponding torque.

In this context it is further conceived that the control device isconfigured such that by the gripping device open or closed samplecontainers may be submitted to the closing device and may be taken outof it. To this end, the gripping device may be configured such thatseparated unused closed elements or used closing elements detached fromthe sample containers are grippable and are moved to the closing deviceand away from it. The gripping device may also be used to finally removean already detached closing element from the corresponding samplecontainer, for example in case of a screw closure, by conducting atleast a part of a rotation of the closing element with respect to thesample container. Naturally, the gripping device may also in the reversecase place a closing element on the sample container during closing of asample container and then, for example by at least a part of arevolution, generate an primary engagement between the closing elementand the sample container. However, in this process it is not consideredthat the gripping device serves to detach a closing element under use ofa high torque from its fixedly screwed position or to tighten it into afixedly screwed position.

Preferably, the sample processing device is configured such that the atleast one pipetting device is moveable with respect to a samplecontainer, contained in the closing device and opened, to be able toextract sample liquid from the corresponding sample container.

Further it is proposed that the sample processing system comprises atleast one closing element carrier, by means of which unused closingelements can be or are provided on the receiving plate.

The sample processing system may further comprise a disposal containerfor disposing of used pipetting tips and/or used closing elements,wherein preferably the disposal container is arranged in particularhanging at a third edge of the receiving plate, which runs along thesecond direction. As disposal container a bag-like container made ofplastic may be used, but also box-shaped containers with firm walls areconceivable.

The gripping device comprises preferably a plurality of moveablegrippers, which are configured such that sample containers or closingelements can be gripped from outside by means of the grippers. In apreferred embodiment four grippers are provided which are arranged alongthe circumferential direction distributed in 90° steps. However, alsoless or more than four grippers are conceivable. The grippers arepreferably formed such that different types of sample containers orcorresponding closing elements can be gripped, rotated and transportedby them. The grippers may hence be used unchanged for the processing ofdifferent sample containers and their closing elements, such as theknown containers PreserCyt® ampoules, SurePath™ ampoules or PCR Mediatubes. Naturally, to allow for this, the control device is configuredsuch that the gripping device or its grippers may be controlled suchthat different sample containers may be gripped by the grippers.

The sample processing system may further comprise an incubator device,which is arranged at the receiving plate and in which a plurality ofsample containers may be accommodated. The incubator device allows forpreparing steps, in particular for a DNA analysis, for example to beable to denature DNA-strands.

Preferably, the sample processing system comprises a loading devicemoveable towards the receiving plate along the first direction (X),wherein the loading device is configured such that it moves pipettingtip carriers and/or closure carriers and/or sample container carriersand/or further carriers necessary for the sample processing along thesecond direction (Y) towards the receiving plate or away from it,wherein preferably the loading device is moveable along a second edge ofthe receiving plate, which is opposite to the first edge. The loadingdevice allows manual providing of carriers of every type outside of thereceiving plate and hence also outside of the sample processing deviceand an automated in- or out-driving of carriers with pipetting tips,sample containers or closing elements.

The loading device comprises preferably a second sensor unit by means ofwhich an identification pattern, in particular a barcode, of a pipettecarrier and/or a closure carrier and/or a sample container carrierand/or a further carrier is detectable, and/or by which anidentification pattern, in particular barcode, of at least one samplecontainer accommodate in a sample container carrier is detectable. Dueto this it is possible that carriers provided and filled manually may becontrolled and a correct filling of the sample processing device may becontrolled by means of the control device. Further, it may also bedetermined which types of sample container carriers have been loadedwith which type of sample containers, to be, for example, able toperform the control of the gripping device according to the type ofsample containers.

As a further development it is proposed that the number of pipettingdevices attached to the first working arm is the same as the number ofgripping devices on the second working arm, wherein the number ispreferably one to four. If several pipetting devices or gripping devicesare present, several sample containers may be processed simultaneously.

In an exemplary filling or configuration of the sample processing systemit is conceivable that on the receiving plate along the first direction(X) in direction from the first working arm to the second working armare arranged:

-   -   a pipetting tip carrier with a plurality of pipetting tip        frames, preferably five pipetting tip frames with 96 pipetting        tips each arranged next to each other along the second direction        (Y);    -   preferably an incubator, in particular suitable for        accommodating 24 sample containers of a specific type;    -   preferably at least one closing element carrier with unused        closing elements for a specific type of sample container;    -   preferably a container for a reagent, in particular a        lysis-buffer;    -   at least one sample container carrier for a sample of a second        type, preferably a plurality of sample container carriers for 24        sample containers of the second type, each:    -   at least one sample container carrier for a second or third type        of sample container, preferably a plurality of sample container        carriers for 12 sample containers of the first type, each, or        for 6 sample containers of the third type each;    -   a sample container carrier for sample containers of the first or        the third type;    -   a sample container carrier for sample containers of the second        type;    -   at least one closing device, suitable for sample containers of        the first and the third type, preferably for such closing        devices next to each other along the second direction (Y).

The sample containers of the first type may for example to sureSurePath™ ampoules. As sample container of the third type PreservCyt®ampoules are considered. The PCR Media tubes may be used as samplecontainers of the second type. This distribution of specific samplecontainers to the claimed types is purely exemplarily and samplecontainers may also be used, which are known under other desigantions ortrade names.

To this end, it is proposed as a further development that the sampleprocessing system comprises at least one further closing device,configured for sample containers of the second type, preferably for suchclosing devices next to each other along the second direction (Y).Hence, within the sample processing system sample containers of at leasttwo different types may be opened or closed by respective closingdevices. In interrelation with the gripping device, which is able togrip, transport and rotate all types of sample containers, a flexiblyuseable sample processing system results, which may also be adapted toodifferent processing methods.

Further, a processing method for biological samples, in particularbodily fluid as blood, saliva, secretions and the like or tissue samplesis proposed, comprising the steps:

providing of at least one sample container carrier with at least oneclosed sample container containing a biological sample;

moving the at least one sample container carrier on a receiving plate ofa sample processing device;

wherein the method according to the invention comprises the followingsteps, which are preferably performed repeatedly until each samplecontainer has been processed:

gripping of the or a sample container with a gripping device of thesample processing device;

mixing of the sample liquid contained in the sample container, inparticular of liquid biological material or of a mixture of at least onereagent with at least partially the solved biological material, byrotating the sample container with the gripping device, preferably withabout 500 to 2000 revolutions per minute; andplacing of the sample container at a desired position within the sampleprocessing device by means of the gripping device for furtherprocessing.

The processing method comprises preferably the following further steps,which are preferably performed repeatedly until each sample containerhas been processed:

placing the sample container into a closing device;

detaching of a closing element of the sample container accommodatedwithin the closing device by means of the closing device;

removing the detached closing element from the sample container and fromthe closing device by means of the gripping device; and

preferably rotating the closing element by means of the gripping elementafter detaching by the closing device and before removing of the closingelement, to cancel an engagement between the closing element and thesample container possibly effective after the detaching.

As further development it is proposed that in the processing method atleast one pipetting tip carrier with unused pipetting tips is providedand that the at least one pipetting tip carrier is moved on thereceiving plate of the sample processing device.

Further, the processing method may comprise the following steps, whichare preferably performed repeatedly until each sample container has beenprocessed:

collecting a pipetting tip from the pipetting tip carrier by means of apipetting device;

aspirating a desired amount of sample liquid from a specific samplecontainer;

dispensing the sample liquid accommodated in the pipetting tip intoanother, empty sample container; and

disposing the used pipetting tip.

These processing steps may in particular be an aliquotation. In theprocess of aliquotation a partial amount to be analyzed (aliquotatedpart) may be taken out from the total amount of a sample contained inthe sample container and be put into a further sample container,preferably by pipetting. In the process of aliquotating also only apartition of an entire sample into several samples may be performed,wherein the taken-out sample (aliquot) is not necessarily the one thatis analyzed, one may also speak of a kind of portioning.

In addition it is proposed that the processing method comprises furtherthe following steps, which are preferably performed repeatedly untileach of the sample containers has been processed:

replacing of the beforehands removed used closing elements on or placingof an unused closing elements onto the sample container located withinthe closing device by means of the gripping device;

closing of the sample container located within the closing device bymeans of the closing device;

preferably rotating the closing element by means of the gripping deviceafter the replacing by the gripping device and before the closing of theclosing elements to generate after placing of the closing element aprimary engagement between the closing element and the sample container;removing the reclosed sample container on the closing device by means ofthe gripping device;placing of the reclosed sample container, in particular in samplecontainer carriers, preferably into the sample container carrier fromwhich the sample container has been taken out.

Within the processing method the closed sample container, whichcomprises the biological probe, may be a sample container of a firsttype, wherein the method may further comprise the following steps:providing of at least one unclosed, preferably empty sample container ofa second type in a corresponding sample container carrier, wherein onthe sample containers of the first and the second type an identificationpattern, preferably barcode, is attached and wherein always two samplecontainers of the first and the second type comprise an identicalidentification pattern.

To this end, it is proposed as a further development that duringmovement of the sample container carrier with the sample containers ofthe first and the second type the identification patterns on the singlesample containers and preferably on the sample container carriers aredetected and stored and wherein it is compared, whether to each samplecontainer of the first type a sample container of the second type withidentical identification pattern is present.

During placing of the sample container into the sample container carrierthe identification pattern attached to the sample container may bedetected by means of a sensor unit on the gripping device and the samplecontainer may be placed in a predetermined rotation position withrespect to the rotation position in which the identification pattern hasbeen detected into the sample container carrier such that a plurality ofsample containers placed by means of the gripping device into the samplecontainer carrier are aligned with respect to their respectiveidentification pattern essentially in the same manner.

In the processing method the empty sample container, into which thesample liquid is dispensed, may be a sample container of the secondtype.

Preferably, in the processing method the providing steps are performedoutside of the sample processing device on a providing surface upstreamof the sample processing device.

Further, the processing method may also comprise the steps: automatedmoving of the sample container carriers from the receiving plate of thesample processing device to the providing surface and manual takeout ofthe sample container carriers.

Additionally, it is proposed for the processing method that a closingelement carrier with unused closing elements for sample containers isprovided, in particular for sample containers of the second type.

To this end, the closing element carrier may be positioned manually onthe receiving plate of the sample processing device.

The mixing of sample liquid in a sample container by means of thegripping device is preferably performed after a transport of the samplecontainer into the region of a disposal container.

In the following, the invention will be described exemplarily andnon-restrictingly with respect to an embodiment.

FIG. 1 shows a schematic perspective view of an embodiment of a sampleprocessing device of a sample processing system.

FIG. 2 shows a schematic perspective view of a possible configuration ofthe sample processing system with further components of the system addedto the sample processing device such as sample containers and theircarriers as well as pipetting tips and their carriers.

FIG. 3 shows in a schematic enlarged perspective view an embodiment of agripping device of the sample processing device.

FIG. 4 shows in a schematic and simplified top view a configuration of asample processing system for a processing method for opening/closing ofsample containers of different types.

FIG. 5 shows in a schematic and simplified top view anotherconfiguration of the sample processing system for a processing methodfor opening/closing of sample containers of different types.

FIG. 6 shows in a schematic and simplified top view a configuration ofthe sample processing system for a processing method for aliquotation ofsamples.

FIG. 7 shows in a schematic and simplified top view a configuration ofthe sample processing system for a processing method or aliquotation andfurther processing of samples.

FIG. 1 shows in a schematic, perspective view a sample processing system10 with a sample processing device 12. The sample processing device 12comprises a receiving plate 14, which is arranged via a not illustratedbasic construction on a substrate. The basic construction may beconnected with the sample processing device 12 or may be a separateelement, such as a table or the like. The receiving plate 14 forms aplane, which extends into a first direction X and a second direction Y.Along a first edge 18 of the receiving plate two working arms 20 and 22are arranged which are movable along the X direction. These two workingarms 20, 22 are driven by not illustrated driving devices and aresupported moveably or rollingly such that they may be moved relative tothe receiving plate 14. The working arms 20, 22 each comprise a verticalsupporter 24 and 26 (partly covered) supported on the receiving plate 14and a horizontal supporter 28 and 30 attached thereon. The horizontalsupporters comprise on the ending, which is opposite to the verticalsupporters 24, 26, a rolling supporter 32, 34, which points upwards intoa third direction Z, which is engaged via rolls 36 with anon-illustrated guidance. The guidance is part of a not illustratedframe construction of the sample processing device 12. Such a frameconstruction is provided above the receiving plate 14 and may alsocomprise a housing with walls and openings not illustrated at thisplace.

On the first working arm 20 a plurality of pipetting devices 40 arearranged next to each other along its horizontal supporter 28. Allpipetting devices 40 are moveable with respect to the horizontalsupporter 28 along the Y direction. Further, each pipetting devicecomprises a pipetting channel 42, which is additionally moveable alongthe vertical Z direction. Each pipetting device may be controlled via anon-illustrated control device, such as a desktop computer or anotebook, on which a corresponding control program is installed, to beable to perform automated pipetting processes. The four pipettingdevices 40 illustrated here in the example—it may also be less ormore—may be controlled separately to arrive at their possible or desiredpositions along the horizontal supporter 28 to position a correspondingpipetting channel 42 in the Z direction and to be able to aspirate ordispense a desired amount of liquid.

On the second working arm 22 a plurality of gripping devices 50 arearranged next to each other along its horizontal supporter 30. Allgripping devices 50 are moveable with respect to the horizontalsupporter 30 along the Y direction. Further, each gripping device 50comprises a gripping means 52 covered in FIG. 1 (see FIG. 3), which ismoveable also in the vertical Z direction. Each gripping device may becontrolled by means of a not illustrated control device, such as adesktop computer or notebook, on which a corresponding control programis installed, to be able to perform automated gripping processes. Thefour gripping devices 50 illustrated exemplarily here—it may also beless or more—may be controlled separately to arrive at their possible ordesired positions along the horizontal supporter 30 and to positioncorresponding gripping means 52 along the Z direction.

Further, on the receiving plate 14 closing devices 60 and 62 arearranged on its right edge in FIG. 1. At a specific position in the Xdirection a plurality of closing devices 60 or 62 are arranged next toeach other along the Y direction, in the present example four closingdevices 60, 62, each. This number of arranged closing devices is onlyexemplarily, it may also be provided more or less closing devices 60,62. The closing devices 60, 62 are configured to detach closures, inparticular screw closures, from sample containers or to tighten them onthese. To this end, the four closing devices 60 may for example beconfigured for a type of sample container and their closing elements(cap) and the four closing devices 62 may be provided for a differenttype of sample container and their closing elements (caps). The numberof closing devices 60 or 62 corresponds hence to the number of pipettingdevices 40 or the number of gripping devices 50 or a multiple thereof.This allows approximately synchronous processing of a number of samplecontainers, which corresponds to the number of pipetting devices 40 orgripping devices 50.

Along the Y direction a loading surface 16, which extends along a secondedge 19 of the receiving plate 14, is arranged in front of the receivingplate 14. On this loading surface materials to be processed may beprovided. By means of a loading device 70 materials arranged onrespective carriers may be moved along the Y direction from the loadingsurface 16 to the receiving plate 14 or may be removed therefrom again.To this end, the loading device 70 comprises a carrier drive 72, whichis able to engage by means of a gear wheel into a gear rod formed on acarrier (not illustrated). The loading device 70 is also moveablerelative to the receiving plate 14 and to the loading surface 16 alongthe X direction and comprises to this end a corresponding notillustrated driving unit. Further, it has to be noted that on theloading device a sensor device 74 is attached, by means of whichidentification patterns at the used materials, such as barcodes, may bedetected, read and be transferred to the not illustrated control device.The control device is also configured to control the movements of theloading device 70 and the movements of material carriers by means of theloading device 70.

Further, on the right edge 21 of the receiving plate a frame 37 isindicated, which delimits an opening 38. On this frame 37 for example abag of plastic may be attached as non-illustrated disposal container.Conceivable is also the arrangement of a non-flexible disposal containerwith firm walls (for example a box). According to the configuration ofthe sample processing system the disposal container may also be arrangedon a position of the receiving plate 14 or the sample processing device12, suitable for the sample processing processes.

FIG. 2 shows a schematic illustration of the sample processing system 10similar to FIG. 1, wherein on the receiving plate 14 of the sampleprocessing device 12 further components of the sample processing system10 are arranged in an exemplary manner. With respect to FIG. 2 on theleft most a pipetting tip carrier 44 is arranged, into which a pluralityof pipetting tip frames 46 is accommodated. In the respective pipettingtip frame 46 a plurality of pipetting tips 48 is arranged preferably inmatrix shape. The pipetting tips 48 may be connected with the pipettingchannel of a corresponding pipetting device 40 automatically to be ableto perform a pipetting, i.e. aspirating and dispensing of liquid. Thepipetting tip carrier 44 illustrated here may accommodate up to fivepipetting tip frames 46. A pipetting tip frame comprises in the presentexample ninety-sixth (96) pipetting tips 48 in a 8×12 matrixarrangement. Naturally, also different pipetting tip frames with adifferent number of pipetting tips may be accommodated in one suchpipetting tip carrier.

Carriers 64 and 66 neighboring the closing device 60 sample container onthe left side are illustrated in place of a plurality of samplecontainers not shown in this illustration. A simplified example of asample container 68 is illustrated in FIG. 3. As sample container thecommonly known sample containers may be used, such as PreserCyt®ampoules, SurePath™ ampoules or PCR Media tubes. The illustrated exampleof FIG. 2 shows a configuration according to the schematic arrangementof FIG. 7. The sample container carriers 64 are here configured forsample containers 68 of a first type, such as PerserCyt® ampoules orSurePath™ ampoules. The sample containers carrier 66 are provided forsample containers 68 of a second type, such as PCR Media tubes. Thesample containers of the different types have different dimensions,which is illustrated by the differently large reception openings 64-1and 66-1 for sample containers in the sample container carriers 64, 66.

The sample processing system 10 further comprises in the illustratedconfiguration an incubator 80, in particular configured for samplecontainers of the second type. Within incubator 80 a sample container 68is exemplarily indicated, which is closed by means of a closing element(cap, stopper) 67. The incubator is arranged next to the pipetting tipcarrier 44. Next to the incubator 80 closing element carriers 82 forunused closing elements, such as screw closers, are arranged. Here,these closing element are not illustrated. Exemplarily, it is referredto the closing element illustrated in FIG. 3, which closes the samplecontainer 68. The, in particular, stacked closing elements (caps)accommodated in the closing element carrier 82 may be provided forrespective sample containers of differing types. Between the closingelement carriers 82 and the first sample container carrier 66 is furthera liquid container 84 arranged, in which a reagent may be comprised suchas a lysis buffer or the like.

FIG. 3 shows in enlarged schematic perspective view a gripping device 50of the sample processing system 10 or the sample processing device 12.As already mentioned the gripping device 50 comprises a gripping means52. This gripping means 52 comprises in the present example fourseparate grippers or gripping arms 54, which may be swivelled around acorresponding swivel axis SA. Due to this rotatability the grippers 54,in particular their gripping sections 55, may be moved towards eachother and away from each other, to grip a sample container 68 and/or aclosing element 67 or to let them loose. The gripping means 52 isprovided with a not-visible rotary drive to be able to rotate thegripping means 52 and the grippers 54 around a gripper axis of rotationGA. With 56 a driving device is indicated, which effects via an axle 58connected with the gripping means the swivelling of the gripping arms54. The whole gripping device 50, in particular also the not-visiblerotary drive of the gripping means 50 and the driving device 56, arewith respect to a stationary gripper basis 53 moveable along the Zdirection. The gripper basis 53 is arranged moveably along the Ydirection on the horizontal supporter 30 of the second working arm 23.The movement of the gripping means 52 along the Z direction is performedby means of a further drive 59. It should be noted that the basicstructure of the gripping device, in particular its gripping basis 53,may comprise a similar or the same structure as the basic structure of apipetting device 40.

The gripping device 50 is connected with the not illustrated controldevice of the sample processing system and is controlled by it. Due tothe control sample container 68 or closing element 67 may be gripped andheld. Further, the control device is configured to cause a rotation ofthe gripping means 52, wherein a gripped sample container 68 or agripped closing element 67 are also rotated simultaneously. This may onthe one hand be used for aligning of sample containers 68 and on theother hand for mixing of a sample liquid within the sample container.The mixing of sample liquid is in this process preferably performed withabout 500 to 2000 revolutions of the gripping means 52 per minute.

The rotatability of the gripping means 52 allows aligning of a grippedsample container 68 such that an identification pattern 90 attached tothe sample container 68, such as a barcode, may be detected by means ofa sensor device 51 provided on the gripper basis 53. Therefore, it ispossible to determine, which sample container 68 is processed by thegripping device 50. Further, due to this it is also possible, to bring agripped sample container 68 in a defined rotation position with respectto a position in which the barcode of the sample container may bedetected from the sensor device 51. If one takes such a position asreference, the sample container may be brought into a desired relativerotation position and be kept in this position, in order to place forexample the sample container 68 in this specific rotation position intoits sample container carrier 64, 66. This allows the essentiallyidentical alignment of all sample containers 68 contained within ansample container carrier 64, 66 such that their barcodes are allpointing into the same direction, preferably in a direction, whichpoints to the sensor device 74 of the loading device 70 (FIG. 1, 2).Hence, the sample containers 68 contained in the sensor device carrier64, 66 or their barcodes 90 may be determined during movement of thesample container carrier 64, 66 out of the sample processing device 10.To this end, the sample container carriers 64, 66 have correspondingrecesses, which make it possible to view the barcodes 90 of the samplecontainers 68. Therefore, the sample containers 64, 66, the singlesample containers 68 or barcodes 90 present on the carriers or thecontainers may be determined during loading of the carriers/containersduring processing of the containers and during unloading of thecarriers/containers without interruption such that it is possible toensure a correct processing.

Moreover, it is also possible that for example a sample container 68,whose barcode 90 is not aligned in the direction of the sensor device 74of the loading device 70 during into the sample processing device 12, isgripped after loading of the sample container carrier by a grippingdevice 50 and that the barcode 90 of the up to now not recognized samplecontainer may be determined later by means of the sensor device 51. Itis hence possible that errors in the initial alignment of samplecontainers 68 in a corresponding sample container carrier 64, 66 may beautomatically corrected.

In the following possible configurations of the sample processing system10 and methods performable by means of these configurations are detailedwith respect to FIGS. 4 to 7. Partly for the purpose of explanationreference signs are used, which are only contained in FIGS. 1 to 3, asthe corresponding components are not illustrated in FIGS. 4 to 7.

FIG. 4 shows an exemplary configuration of an automated opening/closingof sample containers by means of the closing devices 60, 62. In theillustrated configuration it is assumed that up to 8 sample containercarriers 64 each with 12 sample containers of a first type, as forexample of the type SurePath™ (SP) are to be opened or closed. Insteadof SP sample containers also sample containers of a second type, such asPCR Media tubes (CPM) may be loaded, which are to be opened or closed.Conceivable are in particular also mixed arrangements for opening ofclosed sample containers, for example 72 sample containers of the firsttype (SP) in 6 sample container carriers 64 and 96 sample containers ofthe second type (CPM) in corresponding sample container carriers 66,each with 24 sample containers.

First, the sample container carriers 64, 66 are provided manually withclosed sample containers at the loading surface 16. This schematicallyillustrated in a simplified manner by a sample container 64 illustratedby the broken lines. In this providing arrangement the differentcarriers 44, 64, 66 for sample containers, pipetting tips etc. areengaged with holders 65, which are arranged along the providing surface16 in regular distances. The single sample container carriers 64, 66 areconsecutively moved by means of the loading device 70 along the Ydirection from the loading surface 16 to the receiving plate 14. In thisprocess, the loading device 70 moves after each loading of a samplecontainer carrier a bit along the X direction to be able to load thenext sample container. As soon as all sample container carriers 64, 66to be processes are loaded, the opening of the sample containers maystart. To this end, the right (second) working arm 22 and the grippingdevice 50 attached thereon are controlled. One sample container isgripped by each gripping device 50, here exemplarily four grippingdevices, and removed out of the sample container carrier 64, 66 (liftedupwardly). In this process, the barcode 90 at the respective samplecontainer 68 may be read by means of the sensor device 51 on thegripping device 50. Consecutively, the gripped sample containers areplaced into the closing device 60 in dependence of their type, inparticular sample containers of the first type (SP), or in the closingdevice 62, in particular sample containers of the second type (CPM). Thesingle closing devices 60, 62 detach from the sample containeraccommodated therein the corresponding closing element (preferably screwclosure or cap). As soon as the closing elements are nearly completelydetached, they may be gripped by the respective gripping devices and ifnecessary they may be completely screwed off, for example by one partialrevolution of the gripping means 52 and the grippers 54 around thegripper axis of rotation 54. The gripped closing elements may then beremoved from the sample containers and be transported to a disposalcontainer indicated two-dimensionally by 39. As soon as the grippingdevice has reached a position above the disposal container 39, theclosing elements may be let loose and drop into the disposal container39. Consecutively, the gripping devices are moved again to the nowopened sample containers in the respective closing devices 60, 62, inorder to grip the open sample containers and to remove them from theclosing devices 60, 62. The opened sample containers are hereafterplaced again into a sample container carrier 64, 66, preferably eachopen sample container is transported to its original position, fromwhich it has been taken out in closed state from the sample containercarrier. During transportation or placing of the opened samplecontainers the barcode 90 provided at the sample containers may be readby using the sensor device 51, on the one hand to ensure the correctprocessing and on the other hand to be able to place the samplecontainers by movement into a specific rotation position in an alignedposition into the sample container carrier, i.e. all sample containersare essentially aligned in the same manner such that their respectivebarcodes may be captured by the sensor device 74 of the loading device70.

In the process of closing of open sample containers these are providedin sample container carriers 64, 66 on the loading surface 16 and loadedby means of the loading device 70. Consecutively, open sample containersare gripped by means of the gripping devices on the second working armand placed into the closing devices 60, 62. Afterwards, the grippingdevices are moved to the closing element carrier 82, on which unusedclosing elements are provided for the sample containers to be closed.The closing element carrier(s) have been arranged, preferably manually,beforehands within the sample processing device, i.e. on the receivingplate. The gripping devices grippe an unused closing element, each, andtransport it to a corresponding open sample container within the closingdevices 60, 62. By means of the gripping device the closing elements areput onto the respective sample container and preferable by means of atleast one partial revolution loosely screwed onto the sample container,to allow a first engagement between the closing element and the samplecontainer. Consecutively, the closing elements are let loose by thegripping devices such that the closing devices may tightly close thesample containers with the closing element. The then closed samplecontainers are taken out from the closing devices 60, 62 by means of thegripping devices and transported again to a sample container carrier.Preferably each closed sample container is transported to its originalposition, from which it has been taken out in open state from the samplecontainer carrier 64, 66. During transportation or placing of the openedsample container the barcode provided at the sample containers may beread, to on the one hand ensure the correct processing and on the otherhand to be able to place the sample container in aligned position withinthe sample container carrier, i.e. all sample containers are alignedessentially in the same manner such that their respective barcodes canbe captured by the sensor device 74 of the loading device 70.

After opening or closing of all loaded sample containers, the samplecontainer carriers 64, 66 with the completely processed samplecontainers (opened or closed) are moved by means of the loading device70 from the receiving plate to the loading surface 16 (in Y direction),where they are preferably taken out manually and be delivered toprocessing steps, if necessary, in neighbouring further sampleprocessing devices. It is obvious that the aforementioned steps by meansof which the sample containers may be opened or closed, are performedrepeatedly, since per cycle in the present example four samplecontainers may be processed quasi synchronously. If for example 96sample containers are to be processed, 24 cycles with 4 samplecontainers have thus to be performed until a sample containers arebrought from the opened to the closed state (or vice versa). Withinthese repeated steps performed by means of the second working arm or thegripping devices and the closing devices the method steps of loading andunloading of sample container carriers 64, 66 by means of the loadingdevice are not included, also if the loading device naturally performsseveral loading or unloading processes after each other or is able to doso.

FIG. 5 shows a configuration for opening/closing of sample containerssimilar to FIG. 4. Here, however, sample containers of a third type areexemplarily considered, from which in one sample container carrier 64only six exemplars can be placed. For the sample containers of the firsttype (SP) and the third type (PC) preferably the same sample containercarriers 64 may be used. However, instead of 12 sample containers of thefirst type (SP) only six sample containers of the third type (PC) may beaccommodated, respectively, i.e. between two neighbouring samplecontainer of the third type (PC) exists a free space. With theillustrated configuration it is possible to open up to 60 samplecontainers of the third type (PC) or to close them with unused closingelements suitable for this type of sample container. The process is thesame as described above with respect to FIG. 4 for the therein describedsample containers of the first and the second type.

In processing methods for which by means of the sample processing systemonly an opening or closing of sample containers has to be performed,normally no pipetting tips are used and also the optional incubator isnot used. Typically, also the first working arm 20, which is illustratedin FIGS. 4 and 5 on the left side in its standby position, with thepipetting devices provided thereon, is not necessary.

In this respect it is conceiveable to provide gripping devices also onthe first working arm instead of the pipetting devices. This wouldresult in a processing device, which could by means of two working armsand gripping devices attached thereon perform opening/closing of samplecontainers faster, since the processing steps to be performed have notbeen carried out from one working arm with gripping devices, but couldbe distributed optimized to both working arms.

FIG. 6 shows a configuration of the sample processing system forperforming a method for aliquotation of samples, which are contained inthe sample containers. On the loading surface 16 a plurality of samplecontainer carriers 64 with sample containers of a first type (SP) or athird type (PC) are provided. Further, a plurality of sample containercarriers 66 for sample containers of a second type (CPM) are provided inthe same manner. Finally, also a pipetting tip carrier 44 with aplurality of pipetting tip frames 46 and unused pipetting tips 48contained therein are provided. The different carriers 44, 64, 66 forsample containers and pipetting tips are moved by means of the loadingdevice 70 into the direction of the receiving plate 14 such thatafterwards the sample processing device is filled with carriers 44, 64,66. As already described above, the carriers and the sample containersor their barcodes may be captured by means of the sensor device 74 ofthe loading device 70 such that the position of each sample containermay be identified uniquely, in particular taking into account in whichsample container carrier it is accommodated and at which position of thereceiving plate the sample container carrier has been loaded.

Normally, the sample containers of the first (SP) or the third (PC) typecontain the entire sample, from which a aliquot has to be taken. Thesesample containers are typically closed.

In the method a plurality, preferably four, sample containers of thefirst type are gripped by means of the gripping device 50 on the secondworking arm 22 and are moved into the direction of the disposalcontainer 39. When the gripping device with the sample containers hasarrived there, the sample containers are rotated by the gripping meansaround the gripper axis of rotation GA, preferably with about 500 to2000 revolutions per minute, such that the sample in the respectivesample containers may be mixed well. After mixing the sample containersare transported to a respective closing device 60 for this type ofsample container. After placing and releasing of the closed samplecontainers their closing elements (preferably screw caps) are detachedby means of the closing device 60. The detached closing elements aregripped by the gripping devices and removed from the sample containers,wherein gripping devices perform also a (partial) revolution ifnecessary to cancel the already detached engagement between the closingelement and the sample container. Consecutively, the gripping devicesare moved into the direction of the disposal container 39. There, thegripped closing elements are either disposed or they remain in therespective gripping device, to be placed onto the sample containeragain, later.

By means of the first working arm 20 and a pipetting device 40 attachedthereon, pipetting tips (tips) are collected from the correspondingpipetting tip carrier 44. The pipetting tips are coupled automaticallywith the pipetting channels of the pipetting devices in this process.The first working arm is then moved into the direction (X) of theclosing devices. Each pipetting device is arranged above one samplecontainer accommodated in a respective closing device. Consecutively,the pipetting tips are lowered into the respective sample container totake out (aspire) a specific amount, such as 500 or 1000 μl, of thesample. After aspiring the pipetting devices with the pipetting tipscontaining the sample liquid are moved to the corresponding samplecontainers of the second type (CPM) such that an aspirated sample may bedelivered (dispensed) into such an up to now empty sample container.After dispensing the first working arm 20 is moved into the direction ofthe disposal container 39, where the used pipetting tips are ejected anddisposed. Then, the first working arm is moved again into the directionof the pipetting tip carrier 44.

The second working arm 22 may now be moved again from its position inthe region of the disposal container 39 or its standby position at theright edge, as illustrated in FIG. 6, to the closing devices 60, to beable to place the closing elements holded therein again onto the samplecontainers within the closing devices. Alternative to reusing of theseclosing elements, it is also conceivable that these are disposed (intothe disposal container 39) and that unused closing elements arecollected by means of the gripping devices, for example from a positionstill left empty in FIG. 6 between incubator and sample containercarrier 66 for the sample containers of the second type (CPM). Duringplacing the used or new closing elements the gripping devices maygenerate a primary relative loose engagement between closing element andsample container, preferably by a (partial) revolution of the closingelement with respect to the stationary sample container. Then, theclosing elements are left loose by the gripping devices and the closingdevices perform the actual closing of the sample containers bytightening of the closing elements. In the following the (re-)closedsample containers may be gripped by the gripping devices and transportedback to their position within the sample container carrier and may beplaced there. As already described with respect to FIGS. 4 and 5 above,the sample containers may be aligned during placing them again withinthe sample container carriers by using the sensor device 51 on thegripping device 50. For this alignment process within the configurationpresented here it may be assumed that a sample container, whose barcodehas been recognized by the sensor device 51, has to be rotated about160° to 220° around the gripping axis of rotation GA, to align thebarcode of the sample container with respect to the direction of thesensor device 74 of the loading device. Of course, according to thearrangement of the two sensor devices 51 or 74 also differing rotationangles are possible or necessary.

After a sample has been extracted in the aforementioned manner from eachsample in a sample container of the first (SP) or the third (PC) typeand an aliquot is contained in a corresponding sample container of thesecond type, the different sample container carriers 64, 66 and thepipetting tip carrier 44 may be removed by means of the loading device70 again from the receiving plate such that they may be taken out againat the loading surface. In particular, the non-closed sample containersof the second type (CPM) with the aliquot are preferably provided tofurther processing steps, in particular in a neighbouring furtherprocessing device for analysis of the biological probe. Within themethod for aliquotation of probes described herein, the incubator 80 isnot used.

FIG. 7 shows a final configuration, in which additionally to theconfiguration according to FIG. 6 also a container 84 with a reagent, inparticular a lysis-buffer, is provided between the closing elementcarrier 82 (here for unused closing elements of sample containers of thesecond type) and sample container carrier 66 for sample containers ofthe second type (CPM). The reagent, preferably the lysis-buffer, may beadded by means of the pipetting devices to the sample containers of thefirst (SP) or the second (CPM) type such that a mixture of biologicalprobe and reagent may be produced, preferably in the sample containersof the second type. The sample containers of the second type, whichcomprise a sample aliquot with reagent, may be closed analogously to themethod described above. Preferably, the closed containers are then putinto the incubator 80, to generate specific chemical reactions withinthe mixture of sample and reagent. After the desired incubation time thesample containers of the second type may be transported again to theoriginal position in the corresponding sample container carrier 66,wherein, if necessary, the closing elements are removed againbehorehands. At the end closed or opened sample containers of the secondtype with a mixture of probe and reagent may be unloaded, which may besubject to further processing steps, if necessary in a further processdevice.

Further, in all configurations the sample container carriers 64′ and 66′should be noted, which are located on the left side of the closingdevices 60, 62 with respect to the figures. These sample containercarriers 64′ and 66′ are empty at the beginning of the different methodsand are only filled with sample containers of the respective types, ifduring processing a problem with a sample container or the samplecontained therein occurs. Such problems may for example be: barcode notrecognizable, error detected during pipetting or the like.

In the presented methods, which are performed with configurationsaccording to FIG. 6 or FIG. 7, for each sample container of the first orthird type a sample container of the second types exists with anidentical barcode such that identical samples are also contained inidentically marked sample containers. By using two separated sensordevices 51, 73 for reading of barcodes during loading/unloading ofsample container carriers and during processing (gripping, mixing,transporting) of the single samples it is possible to capture in anoptimal manner which sample container have been loaded, which samplecontainers have been subjected to which processing steps, and whichsample containers have been unloaded again. Obviously, it is alsocaptured, which sample containers have been identified as defective, ifnecessary, and are located in one of the sample container carriers 64′or 66′.

All configurations or methods have in common that the gripping device isnot only used for mere gripping and transporting of sample containers,but that the gripping device(s) is also configured for detecting ofbarcodes and for alignment of sample containers based on the position,in which the barcode has been read. Further, the gripping deviceaccording to the exemplary configurations of FIGS. 6 and 7 may be usedas a mixer, without the need to transport and put the sample containersinto a special mixing device. All together, according to the proposedsample processing system with one or a plurality of described grippingdevice(s) optimized processing flows result.

The processing steps described above are performed by means of anaccordingly programmed not illustrated control device (computer) of thesample processing system, which is connected with the variouscomponents, such as sensor devices, loading device, working arms,pipetting and gripping devices, as well as to their drives such that anaccording control or regulation of the various components is possible.However, details of the control/regulation are not further detailedhere. Also if not every component is mentioned here, which might becontrolled by the control device it can nevertheless be assumed that allcomponents, which in any kind contribute actively at method steps to beperformed, is connected with the control device.

The invention claimed is:
 1. A processing method for biological samples,comprising the steps: providing at least one sample container carrier,placing at least one closed sample container in which a biologicalsample liquid is contained into the at least one sample containercarrier at an initial rotation position, wherein each of the at leastone closed sample container comprises a closing element; moving the atleast one sample container carrier onto a receiving plate of a sampleprocessing device; gripping the at least one closed sample container inthe at least one sample container carrier by means of a gripping deviceof the sample processing device; mixing the biological sample liquidcontained within the at least one sample container by rotating the atleast one sample container by means of the gripping device; placing theat least one sample container at a desired position in the sampleprocessing device by means of the gripping device; detaching a closingelement of the at least one closed sample container by means of aclosing device and the gripping device of the sample processing devicefor further processing; and closing the at least one sample containerwith the detached closing element or an unused closing element by meansof the closing device after said further processing.
 2. The processingmethod according to claim 1, further comprising providing of at leastone pipetting tip carrier with unused pipetting tips and moving the atleast one pipetting tip carrier onto the receiving plate of the sampleprocessing device.
 3. The processing method according to claim 2,further comprising the following steps: collecting a pipetting tip fromthe pipetting tip carrier by means of a pipetting device; aspirating adesired amount of the biological sample liquid from a specific samplecontainer of the at least one sample container; dispensing thebiological sample liquid accommodated within the pipetting tip into anempty sample container; and disposing of the used pipetting tip.
 4. Theprocessing method according to claim 3, further comprising repeating thesteps.
 5. The processing method according to claim 1, wherein the atleast one closed sample container which contains the biological sampleliquid, is a sample container of a first type and wherein the methodfurther comprises the following steps: providing at least one unclosedsample container of a second type in a second sample container carrier,wherein the second sample container carrier is distinct from the atleast one sample container carrier, wherein the at least one closedsample container of the first type comprises an identification patternthe at least one unclosed sample container of the second type comprisesthe identification pattern.
 6. The processing method according to claim5, wherein the at least one unclosed sample container of the second typeis empty.
 7. The processing method according to claim 5, comprisingdetecting and storing the identification pattern on the at least oneclosed sample container.
 8. The processing method according to claim 7,further comprising: detecting, by means of a sensor on the grippingdevice, the identification pattern; and wherein placing the at least oneclosed sample container at a desired position in the sample processingdevice by means of the gripping device comprises placing the at leastone closed sample container in a predetermined rotation positionrelative to the initial rotation position, wherein the predeterminedrotation position aligns with rotation positions of a plurality of theat least one sample container placed into the at least one samplecontainer carrier.
 9. The processing method according to claim 7,wherein the at least one unclosed sample container of the second type isempty.
 10. The processing method according to claim 1, wherein saidproviding step is performed outside of the sample processing device on aproviding area in front of the sample processing device.
 11. Theprocessing method according to claim 1, further comprising the steps:automated moving of the at least one sample container carrier from thereceiving plate of the sample processing device to a providing surfaceof the sample processing device and manually taking out the at least onesample container carrier from the sample processing device.
 12. Theprocessing method according to claim 1, further comprising providing aclosing element carrier with unused closing elements for the at leastone sample container.
 13. The processing method according to claim 12,further comprising manual positioning of the closing element carrier onthe receiving plate of the sample processing device.
 14. The processingmethod according to claim 1, wherein mixing of the biological sampleliquid in the at least one sample container is performed by means of thegripping device after transport of the at least one sample containerinto a region of a disposal container.
 15. The processing methodaccording to claim 1, further comprising repeating the steps.
 16. Theprocessing method according to claim 1, wherein the step of detaching aclosing element of the at least one closed sample container comprisesthe following steps: placing the at least one sample container into saidclosing device; generating a loose engagement between the closingelement of the at least one sample container accommodated within theclosing device by means of the closing device; and detaching the looselyengaged closing element from the at least one sample container and fromthe closing device by means of the gripping device; thereby canceling anengagement between the closing element and the at least one samplecontainer.
 17. The processing method according to claim 16, wherein thestep of closing the at least one sample container with the detachedclosing element or an unused closing element comprises the followingsteps: placing the previously detached closing element or placing anunused closing element onto the at least one sample container locatedwithin the closing device by means of the gripping device; looselyscrewing the closing element onto the at least one sample container bymeans of the gripping device conducting at least one partial revolutionof the closing element; reclosing the at least one sample containerlocated within the closing device by means of the closing device;removing the resulting reclosed at least one sample container from theclosing device by means of the gripping device; and placing the reclosedat least one sample container into the at least one sample containercarrier.
 18. The processing method according to claim 17, furthercomprising repeating the steps for a plurality of sample containers, theplurality of sample containers comprising a different set of samplecontainers than the at least one sample container.
 19. The processingmethod according to claim 17, wherein the at least one sample containercarrier comprises a first sample container carrier and a second samplecontainer carrier, wherein placing at least one closed sample containerin which a biological sample liquid is contained into the at least onesample container carrier comprises placing the at least one closedsample container into the first sample container carrier.
 20. Theprocessing method according to claim 16, further comprising repeatingthe steps for a plurality of sample containers, the plurality of samplecontainers comprising a different set of sample containers than the atleast one sample container.
 21. A method for processing a biologicalsample, comprising providing a sample container carrier, placing aclosed sample container into the sample container carrier, wherein abiological sample liquid is contained in the closed sample container,moving the sample container carrier onto a receiving plate of a sampleprocessing device, gripping the closed sample container in the samplecontainer carrier by means of a gripping device in the sample processingdevice, mixing the biological sample liquid contained in the closedsample container by rotating the closed sample container by means of thegripping device, placing the sample container at a desired position inthe sample processing device by means of the gripping device for furtherprocessing, placing the sample container into a closing device,generating a loose engagement of a closing element of the samplecontainer by means of the closing device, removing the loosely engagedclosing element from the sample container and from the closing device bymeans of the gripping device; placing the previously removed closingelement or placing an unused closing element onto the sample containerlocated within the closing device by means of the gripping device;loosely screwing the closing element onto the sample container by meansof the gripping device conducting at least one partial revolution of theclosing element; reclosing the sample container located within theclosing device by means of the closing device; removing the resultingreclosed sample container from the closing device by means of thegripping device; and placing the reclosed sample container into thesample container carrier.